Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.

IF 5.3 2区医学 Q1 IMMUNOLOGY Transplantation Pub Date : 2024-08-01 Epub Date: 2024-07-20 DOI:10.1097/TP.0000000000004985

Jun Shoji, William C Goggins, Jason R Wellen, Patrick N Cunningham, Olwyn Johnston, Shirley S Chang, Kim Solez, Vicki Santos, Tami J Larson, Masahiro Takeuchi, Xuegong Wang

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Abstract

Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS.

Methods: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant.

Results: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study.

Conclusions: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

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Bleselumab 预防肾移植受者原发性局灶性肾小球硬化症复发的有效性和安全性：一项 2a 期随机多中心研究。

背景：局灶节段性肾小球硬化症（FSGS）是终末期肾病的常见病因，在肾移植后经常复发。复发性肾小球硬化症（rFSGS）与不良的异体移植和患者预后有关。Bleselumab是一种全人源免疫球蛋白G4抗CD40拮抗单克隆抗体，它能破坏FSGS中与CD40相关的过程，从而有可能预防rFSGS：这是一项 2a 期、随机、多中心、开放标签研究，研究对象是活体或死体肾移植的成年受者（年龄≥18 岁），且有活检证实的原发性 FSGS 病史。该研究评估了bleselumab联合他克莫司和皮质类固醇作为维持性免疫抑制剂，与他克莫司、霉酚酸酯和皮质类固醇组成的标准治疗（SOC）相比，在预防移植后12个月以上的rFSGS方面的疗效。所有患者都接受了巴利昔单抗诱导治疗。主要终点是rFSGS，定义为移植后3个月内出现蛋白尿（蛋白-肌酐比值≥3.0 g/g），死亡、移植物丢失或失去随访视为rFSGS：结果：63 名患者在移植后接受了 12 个月的随访。与SOC相比，bleselumab治疗3个月后rFSGS发生率相对下降40.7%（95%置信区间，-89.8至26.8；P=0.37；绝对下降12.7%[95%置信区间，-34.5至9.0]）。中央盲法活检复查发现，移植后 3、6 和 12 个月时，rFSGS 的相对（绝对）降幅分别为 10.9% (3.9%)、17.0% (6.2%) 和 20.5% (7.5%)；这些差异无统计学意义。两种疗法的不良反应相似。研究期间无死亡病例：结论：在高危肾移植受者中，与SOC相比，bleselumab在数量上减少了蛋白尿的发生，但在活检证实的rFSGS发生率方面没有观察到明显差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.